A 21-year-old man with a history of schizophrenia is brought to the emergency department by his parents for agitation. Over the last month, the patient has exhibited increasingly odd behavior at home, such as accusing the FBI of sending him threatening messages through the radio. Earlier today, he threatened to kill himself and barricaded his bedroom door so that FBI agents would not find him. The patient has been taking olanzapine daily for the past 3 months under the supervision of his parents. Despite treatment, he has been unable to return to school or work and has persistent delusions of reference as well as recurrent episodes of paranoia, self-isolation, and poor hygiene. The patient has had multiple hospitalizations for similar behavior. He was initially treated with haloperidol, which resulted in muscle spasms and an inability to sit still; the patient was then switched to risperidone with minimal improvement of psychotic symptoms. Physical examination and laboratory evaluation are unremarkable. On mental status examination, he appears restless and makes minimal eye contact. Olanzapine is stopped and a new pharmacotherapy is planned. Which of the following is the most appropriate treatment for this patient?

Question

A 21-year-old man with a history of schizophrenia is brought to the emergency department by his parents for agitation.  Over the last month, the patient has exhibited increasingly odd behavior at home, such as accusing the FBI of sending him threatening messages through the radio.  Earlier today, he threatened to kill himself and barricaded his bedroom door so that FBI agents would not find him.  The patient has been taking olanzapine daily for the past 3 months under the supervision of his parents.  Despite treatment, he has been unable to return to school or work and has persistent delusions of reference as well as recurrent episodes of paranoia, self-isolation, and poor hygiene.  The patient has had multiple hospitalizations for similar behavior.  He was initially treated with haloperidol, which resulted in muscle spasms and an inability to sit still; the patient was then switched to risperidone with minimal improvement of psychotic symptoms.  Physical examination and laboratory evaluation are unremarkable.  On mental status examination, he appears restless and makes minimal eye contact.  Olanzapine is stopped and a new pharmacotherapy is planned.  Which of the following is the most appropriate treatment for this patient?

Quizplus · Accepted Answer

11ec25c8_d7fa_13a9_bc81_03800dcf3757_MD0003_00 Switching antipsychotic medication requires a careful review of the patient's medication history. This patient is treatment-resistant (poor response to ≥2 antipsychotic trials) because he has failed 3 trials, including the first-generation antipsychotic haloperidol and 2 second-generation antipsychotics (risperidone, olanzapine). With the exception of clozapine, there is no evidence that any antipsychotic is more effective than another. Clozapine is unique because it has shown superiority in treatment-resistant schizophrenia and schizophrenia associated with persistent suicidality. Due to the risk of agranulocytosis, clozapine is reserved for patients with treatment-resistant schizophrenia. Other serious adverse effects include seizures, myocarditis, and metabolic syndrome. Despite these concerns, clozapine is recommended by multiple evidence-based guidelines as the treatment of choice for treatment-resistant schizophrenia due to the severe disability associated with this illness. (Choices A, E, and G) Aripiprazole, quetiapine, and ziprasidone are second-generation antipsychotics used in schizophrenia, but they are not as effective as clozapine in treatment-resistant cases. (Choice C) Fluphenazine is a high-potency, first-generation antipsychotic (similar to haloperidol). It is unlikely to be effective in treatment-resistant schizophrenia and has a high risk of extrapyramidal adverse effects (eg, acute dystonic reactions, akathisia). (Choice D) Phenelzine is a monoamine oxidase inhibitor used in treatment-resistant depression. (Choice F) Long-acting, injectable antipsychotics are used in patients who have shown a good response to the oral formulations and are a useful strategy in those who are chronically nonadherent. However, this patient has had a poor response to risperidone. Educational objective: Clozapine is the medication of choice for treatment-resistant schizophrenia and should be considered in patients who have failed ≥2 antipsychotic drug trials. References: Clozapine: balancing safety with superior antipsychotic efficacy. (http://www.ncbi.nlm.nih.gov/pubmed/23006238) Clozapine: a review of clinical practice guidelines and prescribing trends. (http://www.ncbi.nlm.nih.gov/pubmed/24708834)

A 21-Year-Old Man with a History of Schizophrenia Is Brought